This application is part of a 2-site collaborative revised grant with an identical (except for budget/personnel) application submitted concurrently by Dr. Lauren B. Alloy (Temple University). Despite the great public health significance of bipolar disorder (BD), it has been understudied, especially from an integrative biopsychosocial perspective. This application is relevant to NIMH's mission to understand the causes of BD and targets for prevention. Although current work underscores the strong promise of the Behavioral Approach System (BAS) Hypersensitivity Theory of BD, research designs to date are inadequate to determine whether "BAS hypersensitivity" indeed provides vulnerability to BD. Thus, the overarching goal of this application is to use a biobehavioral high-risk design to test whether BAS hypersensitivity, either alone or in combination with BAS-relevant life events, provides vulnerability to first onset of BD during a critical "age of risk." To this end, a large-scale prospective, longitudinal study of 400 (both sites) 15-19 year old individuals (including males and females and Caucasian and minority Ps), selected to be at high vs. low risk for BD based on high BAS (n=200) vs. moderate BAS (n=200) sensitivity, but with no prior history of BD, will be conducted. At Time 1, we will comprehensively assess these Ps' BAS (and BIS) sensitivity vulnerability profiles (with EEG, behavioral task, cognitive style, and self-report), as well as their impulsivity, social/circadian rhythms, lifetime and family history of psychopathology, and current symptoms/impairment. Ps' mothers will also be assessed on BAS (and BIS) sensitivity, as well as their own and the Ps' fathers' history of psychopathology and family history of psychopathology. Ps will be followed prospectively every 6 months with assessments of BAS-relevant life events, cognitions, and social support, and the development of first onsets and recurrences of BD episodes, symptoms, and/or course and progression of their BD. Yearly, we will assess the cyclicity of Ps' BAS locomotor activity and their social/circadian rhythms with 2 weeks of actigraphy. Results will contribute to the development of assessments that may identify individuals with a bipolar endophenotype who are likely to develop BD before such dysfunction occurs and, thus, who can most benefit from early preventive interventions. Finally, the project will contribute to development of BAS-targeted interventions for treatment and prevention of BD. [unreadable] [unreadable] [unreadable]